Sex steroid hormone modulation of NADPH pathways in MCF-7 cells.
Hormonal modulation of glucose-6-phosphate dehydrogenase (G6PD) and of utilization pathways of NADPH generated by G6PD was studied in the MCF-7 human breast cancer cell line, using a quantitative cytochemical method. Our results show that G6PD is increased by 17 beta-estradiol (estradiol) and synthetic progestin (promegestone R5020). The synthetic antiestrogen tamoxifen has no effect on G6PD activity. When it is present in the medium with estradiol, tamoxifen can oppose the stimulatory effect of estradiol on G6PD activity. Mifepristone (RU 38486) has no effect on G6PD activity, but it inhibits the R5020 stimulation of G6PD activity. After MCF-7 pretreatment with estradiol, there is a much stronger stimulation of G6PD activity by R5020. When we studied the effect of the steroid on the two utilization pathways of NADPH generated by G6PD activity, we observed that, in the cells treated with estradiol, there is an increase in reducing equivalents generated by G6PD activity which only affects the NADPH2 pathway, and that there is cell growth stimulation. When tamoxifen is present in the medium, we found no effect on the NADPH utilization pathways, nor on cell growth. In the presence of R5020, the NADPH2 pathway activity is increased but, under our experimental conditions, there was no effect on cell growth. On the other hand, even though RU 38486 is without effect on total G6PD activity, it does cause a modification in the distribution of reducing equivalents: the NADPH2 pathway activity is decreased, while the NADPH1 pathway is stimulated.
Thomas
M
M
Equipe de Reconnaissance des Formes et de Microscopie Quantitative, Université Joseph Fourier, Grenoble, France.
Bader
C
C
Monet
J D
JD
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D009249:NADP / Q000096:biosynthesis*; D009649:Norpregnadienes / Q000494:pharmacology*; D011292:Premedication; D011397:Promegestone / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism
D009649:Norpregnadienes; D013629:Tamoxifen; D015735:Mifepristone; D004958:Estradiol; D009249:NADP; D011397:Promegestone; D005954:Glucosephosphate Dehydrogenase